The main purpose of the proposed work is to investigate the possible role of two oncogenes in the development and maintenance of neoplasia in human\B lineage tumors, with emphasis on pre-B lymphoblastic leukemias. These oncogenes are the transforming gene (abl) found in Abelson murine leukemia virus (A-MuLV) and the transforming gene in DNA from human pre-B leukemias identified by Lane and co-workers. We term the latter gene pbt. We have identified an unusual human pre-B ALL (SMS-SB) in which both these genes appear to be activated. The anatomic presentation of this tumor and its phenotype are both strikingly reminiscent of Abelson lymphosarcoma in BALB/c mice. SMS-SB cells contain an unusually large amount of poly A RNA related to abl, including larger transcripts that are not found in normal cells or in related tumors. DNA from SMS-SB cells transfects NIH-3T3 fibroblasts at high efficiency. Based on these findings, we propose to clone the pbt gene. The organization and expression of abl and pbt will be investigated in normal human and murine B lineage cells at various levels of maturation. The findings will be compared to similar studies of human and murine\B lineage tumors of carefully defined phenotypes. Increased expression will be correlated with ability of tumor DNA to transfect rodent fibroblasts. We will attempt to generate antisera to the gene products of abl and pbt; these antisera will be used to probe the same types of cells for increased expression and to characterize the human gene products. We will transform human hematopoietic cells with appropriate pseudotypes of A-MuLV to test whether v-abl activates pbt in human hematopoietic cells. Finally, we will test both SMS-SB cells and NIH-3T3 cells transformed by DNA from SMS-SB cells for production of transforming growth factors. The relationship between growth factors from these two sources and the possibility that pbt encodes one such factor will be explored.